The Japanese archipelago extends from a subtropical zone to a temperate zone and has a warm climate high in humidity, which is liable to facilitate propagation of fungi such as molds. In addition, due to westernization of clothes, people are now accustomed to wearing shoes on feet. Accordingly, a foot serves as a favorable environment for the propagation of the fungi, leading to mycotic skin diseases that are serious social issues nowadays. Of those, onychomycosis has a low complete cure rate and high relapsing and reinfection rates. Therefore, an effective therapy has been demanded.
Conventionally, treatments mainly using tolnaftate formulations have been conducted on such diseases. In recent years, imidazole-based antifungal agents, such as bifonazole and itraconazole, are mainly used.
As the imidazole-based antifungal agents, there are commercially available imidazole-based antifungal agents such as those represented by the general formula (1) described below, specifically, luliconazole represented by the structural formula (1) below and lanoconazole represented by the structural formula (2) below. The above-mentioned luliconazole is currently the newest imidazole-based antifungal agent, and a commercially available product called “Lulicon” (registered trademark) is also present (e.g., see Patent Document 1 and Patent Document 2).
The luliconazole is an imidazole-based antifungal agent having optical activity, and has a wide antifungal spectrum, in particular, remarkable antifungal activity against dermatophytes. In addition, the luliconazole is also characterized by having extremely high retention property in the stratum corneum, and is a composition thus expected for application to the treatment of onychomycosis. However, nail acts as barrier to penetration of external materials including chemical substances, antifungal agents hardly reaches a region where the pathogenic fungi are present. Therefore, the above-mentioned luliconazole alone is insufficient to exert effects on the onychomycosis.
On the otherhand, asmeans foracceleratingpercutaneous absorption of a material having antifungal activity, such as the above-mentioned luliconazol, benzyl alcohol has been known to be used as a penetration accelerator.
Further, in the field of antifungal agents, in addition to the above-mentioned benzyl alcohol, means for facilitating the agent to proceed into the nail have been known in the art, including: a method of combining materials for softening the nail, such as urea and salicylic acid (e.g., see Patent Document 3 and Patent Document 4); a method using fatty acid ester (e.g., see Patent Document 5 and Patent Document 6); and a method of utilizing absorption-promoting agents, such as higher alcohol, organic base, dimethylformamide (DMF), and dimethyl sulfoxide (DMSO). However, in any of the cases, the effects were not sufficient.
Further, as an attempt to treat onychomycosis by means of a compound represented by the general formula 1 below, a method of forming a reservoir layer by combining a film-forming agent with a polyoxypropylene/polyoxyethylene copolymer (e.g., see Patent Document 9) has been developed, resulting in significant improvement in effect thereof. However, when the nail becomes hard after recovering from the onychomycosis to some extent, there is a disadvantage in that a decrease in effect occurs.
(where X represents a hydrogen atom or a chloride atom)

    Patent Document 1: JP 62-93227 A    Patent Document 2: JP 10-226686 A    Patent Document 3: JP 10-152433 A    Patent Document 4: JP 10-226639 A    Patent Document 5: JP 07-206711 A    Patent Document 6: WO 96/11710    Patent Document 7: JP 06-211651 A    Patent Document 8: JP 2004-529923 A    Patent Document 9: WO 03/105841